Enhanced Immunogenicity of a Conformational Epitope of Human T-Lymphotropic Virus Type 1 Using a Novel Chimeric Peptide
Document Type
Article
Publication Date
12-8-2000
Description
The ability of a peptide vaccine derived from the human T-lymphotropic virus type 1 (HTLV-1) surface envelope glycoprotein protein (gp46) to mimic the native protein and elicit a protective immune response has been examined. This peptide construct, designated MVFMF2, comprises amino acids (aa) 175-218 of gp46 linked by a four residue turn (GPSL) to a promiscuous T-cell epitope from the measles virus fusion protein (MVF, aa 288-302). The peptide was structurally characterized by circular dichroism (CD) spectroscopy and was found to contain α-helical secondary structure. The immunogenicity of MVFMF2 in rabbits and mice was evaluated by direct ELISA and competitive ELISA using peptide constructs and the recombinant protein ACH-RE3 (aa 165-306). This peptide, when administered with adjuvant (N-acetyl-glucosamine-3yl-acetyl-L-alanyl-D-isoglutamine, nor-MDP) was immunogenic in an outbred population of both rabbits and mice. Furthermore, the peptide construct was encapsulated in biodegradable microspheres of poly(D,L-lactide-co-glycolide) to eliminate booster immunization and to examine adjuvant requirements. The data indicate that MVFMF2 shows enhanced immunogenicity when encapsulated in biodegradable microspheres. Inoculation of the encapsulated peptide produced a similar humoral response to that of the free peptide, but did not require the use of adjuvant. Elicited anti-rabbit and anti-mouse antibodies recognized whole viral preparations and the recombinant protein ACH-RE3 in ELISA assays. Additionally, inoculated rabbits exhibited enhanced reactivity to viral antigens by western blot compared to non-vaccinated controls. Although anti-rabbit and anti-mouse antibodies were capable of inhibiting syncytium formation at low dilutions, rabbits were not protected from cell-associated viral challenge. Future development of vaccines to HTLV-1 may need to incorporate the ability to elicit cell-mediated immune responses in order to protect against cell-associated viral infection.
Citation Information
Frangione-Beebe, Melanie; Albrecht, Bjorn; Dakappagari, Naveen; Rose, R. Travis; Brooks, Charles L.; Schwendeman, Steven P.; Lairmore, Michael D.; and Kaumaya, Pravin T.P.. 2000. Enhanced Immunogenicity of a Conformational Epitope of Human T-Lymphotropic Virus Type 1 Using a Novel Chimeric Peptide. Vaccine. Vol.19(9-10). 1068-1081. https://doi.org/10.1016/S0264-410X(00)00340-6 PMID: 11137241 ISSN: 0264-410X